The long-term goal of the proposed research remains the definition of the mechanism of hyperlipoproteinemia in diabetic subjects. Recent results of our studies have suggested that it is the elevated FFA levels of patients with nonketotic diabetes mellitus which leads to increased hepatic very low density lipoprotein (VLDL)-triglyceride (TG) secretion and hypertriglyceridemia. Attempts during the next year will be aimed at lowering the FFA levels in an effort to see if this will restore TG levels to normal in these subjects. In other studies we have evaluated the role played by lipoprotein lipase (LPL) activity in the development of hypertriglyceridemia in ketosis-prone diabetics. Our results indicated that such individuals have a defect in removal of VLDL-TG from plasma, and that decreased LPL activity cannot by itself explain this event. During the next year we plan to investigate the possibility that the removal defect is due to the production of an abnormal VLDL by insulin deficient subjects.